Gene transfer to the salivary glands presents unique challenges, not the least because viral vectors can elicit a strong mucosal immune response. Host immune responses to adenoviral vectors were investigated, following single or multiple administrations to the salivary glands. A strategy was initiated to induce immunological tolerance to adenoviral vectors by feeding animals with inactivated virus particles. It was determined that oral feedings of vector were able to attenuate the host immune response to salivary gland-administered vector, in a dose-dependent manner. This preliminary approach resulted in significantly-increased and prolonged gene expression, even after multiple administrations of vector. The data suggest that relatively specific immune modulation may be achieved to enhance virus-based gene transfer. Progress has also been made with the transfer, expression, and characterization of the antimicrobial protein, histatin 3. It was demonstrated in vitro that histatin 3 was equally effective in killing and preventing germination of azole-resistant and azole-susceptible strains of C. albicans. Sensitive assays were developed to quantitate histatins in biological samples by capillary electrophoresis. The latter has facilitated the initiation of studies of salivary histatin expression in a model of oral mucosal candidiasis. The vector AdCMVH3 is capable of directing the expression and secretion of histatin 3 in vivo.